Functional AGXT2 SNP rs180749 variant and depressive symptoms: Baseline data from the Aidai Cohort Study in Japan.

No study has shown the relationship between alanine-glyoxylate aminotransferase 2 (AGXT2) single nucleotide polymorphisms (SNPs) and depressive symptoms. The present case-control study examined this relationship in Japanese adults. Cases and control participants were selected from those who participated in the baseline survey of the Aidai Cohort Study, which is an ongoing cohort study. Cases comprised 280 participants with depressive symptoms based on a Center for Epidemiologic Studies Depression Scale (CES-D) score ≥ 16. Control participants comprised 2034 participants without depressive symptoms based on the CES-D who had not been diagnosed by a physician as having depression or who had not been currently taking medication for depression. Adjustment was made for age, sex, smoking status, alcohol consumption, leisure time physical activity, education, body mass index, hypertension, dyslipidemia, and diabetes mellitus. Compared with the GG genotype of rs180749, both the GA and AA genotypes were significantly positively associated with the risk of depressive symptoms assessed by the CES-D: the adjusted odds ratios for the GA and AA genotypes were 2.83 (95% confidence interval [CI] 1.23-8.24) and 3.10 (95% CI 1.37-8.92), respectively. The TGC haplotype of rs37370, rs180749, and rs16899974 was significantly inversely related to depressive symptoms (crude OR 0.67; 95% CI 0.49-0.90), whereas the TAC haplotype was significantly positively associated with depressive symptoms (crude OR 1.24; 95% CI 1.01-1.52). This is the first study to show significant associations between AGXT2 SNP rs180749, the TGC haplotype, and the TAC haplotype and depressive symptoms.

Smoking and secondhand smoke exposure and carotid intima-media thickness: Baseline data from the Aidai Cohort Study in Japan.

INTRODUCTION: Epidemiological evidence regarding the relationship between smoking and secondhand smoke (SHS) exposure and carotid intima-media thickness (CIMT) has been limited in Asian populations. Employing baseline data from the Aidai Cohort Study, Japan, we evaluated the evidence in this cross-sectional study. METHODS: Study subjects were 727 men aged 35-88 years and 1297 women aged 34-85 years. Information on smoking, SHS exposure, and confounders was obtained through a self-administered questionnaire. An automated carotid ultrasonography device was used to measure the right and left CIMT. The greatest CIMT measurement in the left or right common carotid artery was considered the maximum CIMT, and a maximum CIMT >1.0 mm was indicative of carotid wall thickening. Age, alcohol consumption, leisure time physical activity, hypertension, dyslipidemia, diabetes mellitus, body mass index, waist circumference, employment, and education level were adjusted at one time. RESULTS: The prevalence of carotid wall thickening was 13.0%. The prevalence of never smoking was 30.5% in men and 90.1% in women. Among those who had never smoked, the prevalence of never SHS exposure at home and work was 74.3% and 48.2% in men and 38.3% and 56.3% in women, respectively. Active smoking and pack-years of smoking were independently positively related to carotid wall thickening regardless of sex, although the association with current smoking in women was not significant. Independent positive relationships were shown between former smoking and pack-years of smoking and maximum CIMT in men but not in women. No significant relationships were found between SHS exposure at home and work and carotid wall thickening or maximum CIMT in either men or women. CONCLUSIONS: Active smoking, especially pack-years of smoking, was positively associated with carotid wall thickening in both sexes. Such positive associations with maximum CIMT were found only in men; however, interactions between smoking and sex were not significant.

Fish and Polyunsaturated Fatty Acid Intake and Carotid Intima-Media Thickness in Japan: the Aidai Cohort Study in Yawatahama, Uchiko, Seiyo, and Ainan.

AIM: Epidemiological evidence regarding the relationship between fish and fatty acid intake and carotid intima-media thickness (CIMT) has been limited and inconsistent. The current cross-sectional study investigated this issue using baseline data from the Aidai Cohort Study. METHODS: Study subjects were 2024 Japanese men and women aged 34-88 years. Right and left CIMT were measured at the common carotid artery using an automated carotid ultrasonography device. Maximum CIMT was defined as the largest CIMT value in either the left or right common carotid artery. Carotid wall thickening was defined as a maximum CIMT value ＞1.0 mm. RESULTS: The prevalence of carotid wall thickening was 13.0%. In men, intake of n-3 polyunsaturated fatty acids (PUFA) was independently positively related to the prevalence of carotid wall thickening, while no associations were found between intake of fish and the other fatty acids and carotid wall thickening or maximum CIMT. In women, intake levels of fish, n-3 PUFA, eicosapentaenoic acid, docosahexaenoic acid, and arachidonic acid were independently inversely associated with carotid wall thickening and intake levels of fish, n-3 PUFA, α-linolenic acid, n-6 PUFA, and linoleic acid were independently inversely associated with the maximum CIMT. No significant relationships were found between intake of total fat, saturated fatty acids, or monounsaturated fatty acids and carotid wall thickening or maximum CIMT regardless of sex. CONCLUSIONS: In women, higher intake of fish and n-3 and n-6 PUFA may be associated with a lower prevalence of carotid wall thickening and a decrease in maximum CIMT.

Functional AGXT2 SNP rs37369 Variant Is a Risk Factor for Diabetes Mellitus: Baseline Data From the Aidai Cohort Study in Japan.

OBJECTIVES: The relationship between alanine-glyoxylate aminotransferase 2 (AGXT2) single-nucleotide polymorphisms (SNPs) and diabetes mellitus (DM) has not been investigated. Therefore, we performed a case-control study to examine this relationship. METHODS: The study subjects included 2,390 Japanese men and women aged 34 to 88 years. In total, 190 cases were defined as having a fasting plasma glucose level ≥126 mg/dL, having a glycated hemoglobin ≥6.5% or currently using diabetic medication. The 2,200 remaining participants served as control subjects. RESULTS: Compared with study subjects with the CC genotype of AGXT2 SNP rs37369, those with the TT, but not CT, genotype had a significantly increased risk of DM: the adjusted odds ratio (OR) for the TT genotype was 1.83 (95% confidence interval [CI], 1.04 to 3.47). AGXT2 SNPs rs37370 and rs180749 were not significantly associated with the risk of DM. The CTA haplotype of rs37370, rs37369 and rs180749 was significantly positively associated with the risk of DM (crude OR, 1.25; 95% CI, 1.01 to 1.56), whereas the CCA haplotype was significantly inversely related to DM (crude OR, 0.53; 95% CI, 0.27 to 0.95). The multiplicative interaction between AGXT2 SNP rs37369 and smoking status with regard to the risk of DM was not significant (p=0.32 for interaction). CONCLUSIONS: This is the first study to show significant associations between AGXT2 SNP rs37369, the CTA haplotype, and the CCA haplotype and DM. No interaction with regard to the risk of DM was observed between rs37369 and smoking.

Relationship between hearing loss and prevalence of depressive symptoms in Japan: Baseline data from the Aidai Cohort study in Yawatahama and Uchiko.

OBJECTIVE: Epidemiological evidence on the relationship between hearing loss (HL) and depressive symptoms, especially in the middle aged, is limited. The present cross-sectional study investigated this issue in middle-aged and older Japanese individuals separately. METHODS: Study subjects were 1018 Japanese adults aged 36-84 years. We used the audiometric definition of HL, which identifies the speech-frequency pure tone average (PTA) hearing thresholds at 0.5, 1, 2, and 4 kHz as an average of four frequencies. HL was defined as present when PTA was > 25 dB HL in the better-hearing ear. Presence of depressive symptoms was defined as a Center for Epidemiological Studies Depression Scale score ≥ 16. Adjustment was made for age, sex, smoking status, alcohol consumption, leisure time physical activity, hypertension, dyslipidemia, diabetes mellitus, body mass index, waist circumference, employment, education, and household income. RESULTS: The prevalence values of HL and depressive symptoms were 11.5% and 15.0%, respectively, among the 575 subjects aged < 65 years and 42.2% and 10.4%, respectively, among the 443 subjects aged ≥ 65 years. Among the 1018 participants, HL was independently related to a higher prevalence of depressive symptoms: the multivariate-adjusted OR was 1.92 (95% CI: 1.19-3.08). This positive association was stronger among middle-aged participants, with a multivariate-adjusted OR of 2.70 (95% CI: 1.34-5.27), but was not significant in the elderly, with a multivariate-adjusted OR of 1.71 (95% CI: 0.83-3.54). CONCLUSION: HL may be positively associated with depressive symptoms in middle-aged, but not older, individuals.

Education and household income and carotid intima-media thickness in Japan: baseline data from the Aidai Cohort Study in Yawatahama, Uchiko, Seiyo, and Ainan.

BACKGROUND: Epidemiological evidence for the relationship between education and income and carotid intima-media thickness (CIMT) has been limited and inconsistent. The present cross-sectional study investigated this issue using baseline data from the Aidai Cohort Study. METHODS: Study subjects were 2012 Japanese men and women aged 34-88 years. Right and left CIMT were measured at the common carotid artery using an automated carotid ultrasonography device. Maximum CIMT was defined as the largest CIMT value in either the left or right common carotid artery. Carotid wall thickening was defined as a maximum CIMT value > 1.0 mm. RESULTS: The prevalence of carotid wall thickening was 13.0%. In participants under 60 years of age (n = 703) and in those aged 60 to 69 years (n = 837), neither education nor household income was associated with carotid wall thickening or with maximum CIMT. Among those aged 70 years or older (n = 472), however, higher educational level, but not household income, was independently related to a lower prevalence of carotid wall thickening: the multivariate-adjusted odds ratio for high vs. low educational level was 0.43 (95% confidence interval 0.21-0.83, p for trend = 0.01). A significant inverse association was observed between education, but not household income, and maximum CIMT (p for trend = 0.006). CONCLUSIONS: Higher educational level may be associated with a lower prevalence of carotid wall thickening and a decrease in maximum CIMT only in participants aged 70 years or older.

Higher number of teeth is associated with decreased prevalence of hearing impairment in Japan.

BACKGROUND/OBJECTIVES: There is limited evidence on the association between tooth loss and hearing impairment (HI). The present cross-sectional study investigated the association between tooth loss and the prevalence of HI in 1004 Japanese adults aged 36 to 84 years. METHODS: HI was defined as present when pure-tone average was > 25 dB at a frequency of 0.5, 1, 2, and 4 kHz in the better hearing ear. Visual oral examinations were performed. Adjustments were made for age, sex, smoking status, leisure-time physical activity, hypertension, dyslipidemia, diabetes mellitus, history of depression, body mass index, waist circumference, employment, education, and household income. RESULTS: Of 1004 study subjects, the prevalence of HI was 24.8% (n = 249). Compared with having 28 teeth, having < 22 teeth, but not having 26 to < 28 or 22 to < 26 teeth, was associated with an increased prevalence of HI; the multivariate adjusted ORs (95% CI) of having 26 to < 28, 22 to < 26, and < 22 teeth were 1.41 (0.85-2.38), 1.51 (0.90-2.57), and 1.96 (1.18-3.30), respectively (p for trend = 0.01). CONCLUSIONS: The results suggest that tooth loss may be associated with an increased prevalence of HI.

Tricks and traps of ICG endoscopy for effectively applying endoscopic transsphenoidal surgery to pituitary adenoma.

Differentiating tumor from normal pituitary gland is very important for achieving complete resection without complications in endoscopic endonasal transsphenoidal surgery (ETSS) for pituitary adenoma. To facilitate such surgery, we investigated the utility of indocyanine green (ICG) fluorescence endoscopy as a tool in ETSS. Twenty-four patients with pituitary adenoma were enrolled in the study and underwent ETSS using ICG endoscopy. After administering 12.5 mg of ICG twice an operation with an interval > 30 min, times from ICG administration to appearance of fluorescence on vital structures besides the tumor were measured. ICG endoscopy identified vital structures by the phasic appearance of fluorescent signals emitted at specific consecutive elapsed times. Elapsed times for internal carotid arteries did not differ according to tumor size. Conversely, as tumor size increased, elapsed times for normal pituitary gland were prolonged but those for the tumor were reduced. ICG endoscopy revealed a clear boundary between tumors and normal pituitary gland and enabled confirmation of no more tumor. ICG endoscopy could provide a useful tool for differentiating tumor from normal pituitary gland by evaluating elapsed times to fluorescence in each structure. This method enabled identification of the boundary between tumor and normal pituitary gland under conditions of a low-fluorescence background, resulting in complete tumor resection with ETSS. ICG endoscopy will contribute to improve the resection rate while preserving endocrinological functions in ETSS for pituitary adenoma.

Clinical features and endoscopic findings of granular cell tumor of the sellar region: A case report and review of the literature.

BACKGROUND: Granular cell tumor (GCT) of the sellar region is a rare tumor of the sellar and suprasellar regions that originate from the neurohypophysis. This tumor is very difficult to differentiate from other pituitary neoplasms, such as pituitary adenoma, pituicytoma, and spindle cell oncocytoma. We report a rare case of GCT arising from the posterior pituitary of the sellar region and suggest a useful indicator for accurate diagnosis and pitfalls for surgical procedures. CASE DESCRIPTION: A 42-year-old woman was admitted to our hospital with bitemporal hemianopsia. Neuroimaging showed a large pituitary tumor in the sellar and suprasellar regions with a hypointense part on T2-weighted magnetic resonance imaging, and the enhanced anterior pituitary gland was displaced anteriorly. Laboratory findings showed mild hyperprolactinemia. Subtotal resection of the tumor was achieved using an endoscopic endonasal transsphenoidal approach. Histological findings showed round or polygonal cells with abundant granular eosinophilic cytoplasm staining strongly for thyroid transcription factor 1. The tumor was, therefore, diagnosed as a GCT of the sellar region, belonging to tumors of the posterior pituitary. After surgery, visual impairment and anterior pituitary function were improved. Follow-up neuroimaging after 1 year showed no signs of recurrence. CONCLUSION: GCT of the sellar region is difficult to diagnose on routine neuroimaging. Therefore, accurate diagnosis requires careful identification of clinical signs, magnetic resonance imaging including hypointensity on T2-weighted imaging, and analysis of combined morphological and immunohistochemical studies.

Association between hypertension, dyslipidemia, and diabetes and prevalence of hearing impairment in Japan.

Epidemiological information regarding the relationship between hypertension, dyslipidemia, and/or diabetes and hearing impairment (HI) has been controversial. The present cross-sectional study investigated this issue in Japan. The subjects were 371 men and 639 women aged 36‒84 years. Hypertension was defined as systolic blood pressure ≥140 mmHg, diastolic blood pressure ≥90 mmHg, or current use of antihypertensive medication. Dyslipidemia was defined as a serum low-density lipoprotein cholesterol concentration ≥140 mg/dL, high-density lipoprotein cholesterol concentration <40 mg/dL, triglyceride concentration ≥150 mg/dL, or current use of cholesterol-lowering medication. Diabetes was defined as a fasting plasma glucose level ≥126 mg/dL, hemoglobin A1c level ≥6.5%, or current use of diabetic medication. HI was defined as present when subjects did not respond to a pure-tone average of >25 dB HL in the better hearing ear. Adjustments were made for age, smoking, alcohol consumption, body mass index, household income, and education. The prevalence of HI was 31.5% in men and 20.8% in women. In men, hypertension, but not dyslipidemia or diabetes, was independently positively associated with HI: the adjusted prevalence ratio (PR) was 1.52 (95% CI: 1.07‒2.16). Having at least two cardiovascular risk factors among hypertension, dyslipidemia, and diabetes was independently positively related to HI: the adjusted PR was 1.82 (95% CI: 1.11‒2.99, P for trend = 0.02). Such positive associations were not found in women. Hypertension and having at least two cardiovascular risk factors may be positively associated with HI in men only.

Advanced fibrosis of non-alcoholic steatohepatitis affects the significance of lipoprotein(a) as a cardiovascular risk factor.

BACKGROUND AND AIMS: Lipoprotein(a) [Lp(a)] is an important independent cardiovascular risk factor. However, Lp(a) levels are lower in patients with chronic liver disease than in healthy subjects. Furthermore, Lp(a) levels decrease as residual liver function declines. Although non-alcoholic fatty liver disease (NAFLD), especially advanced non-alcoholic steatohepatitis (NASH), increases the risk of cardiovascular diseases, the relationship between serum Lp(a) level and NASH is unknown. Thus, we examined the relationship between serum Lp(a) levels and biopsy-proved NAFLD and clarified the significance of Lp(a) measurements for cardiovascular disease screening in patients with NAFLD. METHODS: A total of 176 patients with NAFLD were enrolled. Comprehensive blood chemistry tests and histological examinations of liver samples were conducted. The relationship between serum Lp(a) levels and NAFLD was analyzed. RESULTS: Serum Lp(a) levels in advanced fibrosis (stage 3-4) were lower than those in non-advanced fibrosis (stage 0-2) (p < 0.05). After adjustment for age, sex, body mass index, alanine aminotransferase (ALT), creatinine (Cre), HbA1c level, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), and the use of lipid-lowering agents, the significant inverse association between advanced fibrosis and serum Lp(a) levels remained (p < 0.01). Although the Lp(a) level was inversely associated with an NAFLD Activity Score (NAS) of 5-8, there was no significant association between Lp(a) levels and NAS adjusted for age, sex, body mass index, ALT, Cre, HbA1c level, HDL-C, LDL-C, TG, and the use of lipid-lowering agents. CONCLUSIONS: Advanced NASH is associated with low serum Lp(a) levels; therefore, Lp(a) levels may not be useful in evaluating cardiovascular risk.

Clinical utility of new three-dimensional model using a zero-echo-time sequence in endoscopic endonasal transsphenoidal surgery.

OBJECTIVES: Recognizing the anatomical orientation surrounding the sellar floor is crucial in endoscopic endonasal transsphenoidal surgery (ETSS). Zero-echo-time (ZTE) sequences were recently suggested for a new bone identification technique on magnetic resonance imaging (MRI). This study aimed to evaluate the clinical usefulness of three-dimensional (3D)-ZTE-based MRI models in providing anatomical guidance for ETSS. PATIENTS AND METHODS: ZTE-based MRI and magnetic resonance angiography (MRA) data from 15 consecutive patients with pituitary tumor treated between September 2018 and May 2019 were used to create 3D-MRI models. From these, the architecture surrounding the sellar floor, particularly anatomical relationships between tumors and internal carotid arteries (ICAs), was visualized to preoperatively plan surgical procedures. In addition, 3D-ZTE-based MRI models were compared to actual surgical views during ETSS to evaluate model applicability. RESULTS: These 3D-ZTE-based MRI models clearly demonstrated the morphology of the sellar floor and matched well with intraoperative views, including pituitary tumor, by successively eliminating sphenoidal structures. The models also permitted determination of the maximum marginal line of the opening of the sellar floor by presenting vital structures such as ICAs and tumors. With such 3D-MRI models, the surgeon could access the intracranial area through the sellar floor more safely, and resect the pituitary tumor maximally without complications. CONCLUSION: Our 3D-MRI models based on ZTE sequences allowed distinct visualization of vital structures and pituitary tumor around the sellar floor. This new method using 3D-ZTE-based MRI models showed low invasiveness for patients and was useful in preoperative planning for ETSS, facilitating maximum tumor resection without complications.

Hearing Impairment and Prevalence of Mild Cognitive Impairment in Japan: Baseline Data From the Aidai Cohort Study in Yawatahama and Uchiko.

OBJECTIVES: Hearing impairment (HI) in midlife may increase the risk of dementia. However, epidemiological research on the association between HI and mild cognitive impairment (MCI) is very limited. DESIGN: The present cross-sectional study investigated the relationship between HI and MCI using baseline data from the Aidai Cohort Study. Study subjects were 995 Japanese adults aged 36 to 84 years. We used the audiometric definition of HI adopted by the World Health Organization, which identifies the speech-frequency pure-tone average hearing thresholds at 0.5, 1, 2, and 4 kHz tones. HI was defined as present when pure-tone average was >25 dB HL in the better hearing ear. MCI was defined as being present when a subject had a Japanese version of the Montreal Cognitive Assessment score of <26. Adjustment was made for age, sex, smoking status, alcohol consumption, leisure time physical activity, hypertension, dyslipidemia, diabetes mellitus, history of depression, body mass index, waist circumference, employment, education, and household income. RESULTS: Among the 995 study subjects, the prevalence values of HI and MCI were 24.3% and 44.5%, respectively. HI was independently positively associated with MCI: the multivariate-adjusted odds ratio (95% confidence interval) was 1.86 (1.32 to 2.62). HI was independently related to a higher prevalence of MCI in those aged 60 to 69 years and those aged 70 years or older: the multivariate-adjusted odds ratios (95% confidence intervals) were 1.64 (1.03 to 2.62) and 2.30 (1.04 to 5.27), respectively. CONCLUSIONS: HI may be associated with a higher prevalence of MCI.

Wilson Disease With Giant Splenic Artery Aneurysms Caused by Fibromuscular Dysplasia During Living Donor Liver Transplantation: A Case Report.

Liver cirrhosis can cause splenic artery aneurysms (SAA) that pose a threat to patients undergoing liver transplantation. However, liver transplantation with multiple visceral artery aneurysms including giant SAA caused by arterial fragility has never been reported. We describe a 36-year-old man with decompensated liver cirrhosis due to Wilson disease that was complicated by giant SAA and multiple aneurysms in the bilateral renal arteries caused by fibromuscular dysplasia (FMD). The maximal diameter of the triple snowball-shaped SAA was 11 cm. We planned a 2-stage strategy consisting of a splenectomy with distal pancreatectomy to treat the SAA and subsequent living donor liver transplantation (LDLT) to address the liver cirrhosis. This strategy was selected to prevent fatal postoperative infectious complications caused by the potential development of pancreatic fistula during simultaneous procedures and to histopathologically diagnose the arterial lesion before LDLT to promote safe hepatic artery reconstruction. However, a postoperative pancreatic fistula did not develop after a splenectomy with distal pancreatectomy, and the pathologic findings of the artery indicated FMD. The patient underwent ABO-identical LDLT with a right lobe graft donated by his brother. Other than postoperative rupture of the aneurysm in the left renal artery requiring emergency interventional radiology, the patient has remained free of any other arterial complications and continues to do well at 2 years after LDLT.

The Serum Creatinine Level Might Be Associated with the Onset of Impaired Fasting Glucose: A Community-based Longitudinal Cohort Health Checkup Study.

Objective Skeletal muscle is the main target organ for glycemic control, and the serum creatinine level is a convenient indicator of the skeletal muscle mass. This study aimed to assess the potential relationship between the serum creatinine level and the onset of impaired fasting glucose (IFG). Methods In this large, community-based, retrospective longitudinal cohort study, we examined the records of 7,905 Japanese participants (3,863 men, 4,042 women) of 18-80 years of age who underwent annual health checkups at a single center between April 2003 and August 2013. After applying the exclusion criteria, 6,490 participants were reviewed to identify those with the onset of IFG, defined as a fasting plasma glucose ≥6.11 mM. Among the participants, 278 met the criterion for the onset of IFG during the observation period. Results Creatinine levels were higher in male subjects who exercised periodically and were exercise conscious in comparison to those who did not exercise, and were higher in female subjects who exercised periodically in comparison to female subjects who did not exercise and who were not exercise conscious. Additionally, the serum creatinine level was negatively associated with the onset of IFG in both men [adjusted hazard ratio, 0.98; 95% confidence interval (CI), 0.96-0.99; p=0.008] and women (adjusted hazard ratio, 0.94; 95% CI, 0.91-0.97; p<0.001) after adjustment for variables previously reported to be risk factors for the onset of glucose intolerance and factors associated with chronic kidney disease. Conclusion A low creatinine level might be associated with the onset of IFG. Moreover, the fact that serum creatinine levels increase with exercise might demonstrate the importance of exercise therapy.

Association of household income and education with prevalence of hearing impairment in Japan.

OBJECTIVES/HYPOTHESIS: Epidemiological information regarding the relationship between household income and education and hearing impairment (HI) is limited. The present cross-sectional study investigated this issue in Japan. STUDY DESIGN: Cross-sectional investigation. METHODS: Study subjects were 371 men and 639 women aged 36 to 84 years. A self-administered questionnaire was used. Audiological assessment was performed by pure-tone audiometry. HI was defined as present in subjects who did not respond to a pure-tone average of >25 dB HL in the better hearing ear according to the World Health Organization standard. Adjustment was made for age, smoking status, alcohol consumption, hypertension, dyslipidemia, diabetes mellitus, and body mass index. RESULTS: The prevalence of HI was 31.5% in 371 men and 20.8% in 639 women. In men, a slight inverted J-shaped association was observed between household income and HI, compared with a household income of <3 million yen per year. A household income of 3 to 5 million yen, but not of 5 million yen or more, was independently inversely associated with the prevalence of HI; the prevalence ratio for 3 to 5million yen was 0.73 (95% confidence interval: 0.54-0.999). After adjustment for confounding factors, no relationship was found between household income and the prevalence of HI in women. There were no associations between educational level and the prevalence of HI in either men or women in the multivariate model. CONCLUSIONS: Our results suggest that medium, but not high, household income may be associated with a lower prevalence of HI only in men. LEVEL OF EVIDENCE: 2b Laryngoscope, 129:2153-2157, 2019.

Insulin-like growth factor-1 is inversely associated with liver fibrotic markers in patients with type 2 diabetes mellitus.

AIMS/INTRODUCTION: Insulin-like growth factor-1 (IGF-1) regulates mitochondrial function, oxidative stress, inflammation, stellate cells and insulin sensitivity in the liver, and it might be associated with liver fibrosis from non-alcoholic steatohepatitis. In contrast, type 2 diabetes mellitus is closely associated with the progression from non-alcoholic fatty liver to non-alcoholic steatohepatitis and cirrhosis, so careful evaluation of liver fibrosis is required for patients with type 2 diabetes mellitus. Therefore, we examined the relationship between IGF-1 and liver fibrosis markers in type 2 diabetes patients without obvious alcoholic consumption and determined whether IGF-1 is associated with fibrosis of non-alcoholic fatty liver disease. MATERIALS AND METHODS: We selected 415 patients with type 2 diabetes without obvious alcohol consumption, who were admitted to Uwajima City Hospital between May 2013 and December 2016. We collected and analyzed clinical data to determine correlations between IGF-1 or IGF-1 standard deviation score and fibrosis-4 index or 7S domain of type IV collagen. RESULTS: Multiple linear regression analysis showed that the fibrosis-4 index was inversely correlated with IGF-1 and IGF-1 standard deviation score. Furthermore, the 7S domain of type IV collagen was also inversely correlated with IGF-1 and IGF-1 standard deviation score. CONCLUSIONS: IGF-1 was inversely correlated with liver fibrosis markers in type 2 diabetes mellitus patients without obvious alcoholic consumption. Measuring serum IGF-1 levels might help clinicians to identify type 2 diabetes mellitus patients with advanced non-alcoholic steatohepatitis.

Ipragliflozin Ameliorates Liver Damage in Non-alcoholic Fatty Liver Disease.

BACKGROUND: There are few effective medications for non-alcoholic steatohepatitis (NASH). We investigated the efficacy of ipragliflozin (selective sodium-glucose cotransporter-2 inhibitor [SGLT2I]) for the treatment of patients with type 2 diabetes mellitus (T2DM) complicated by non-alcoholic fatty liver disease (NAFLD). METHODS: We prospectively enrolled patients with T2DM complicated by NAFLD treated at our institutions from January 2015 to December 2016. Patients received oral ipragliflozin (50 mg/day) once daily for 24 weeks. Body composition was evaluated using an InBody720 analyzer. We used transient elastography to measure liver stiffness and the controlled attenuation parameter for the quantification of liver steatosis in patients with NASH. RESULTS: Forty-three patients with T2DM and NAFLD were enrolled (12 with biopsy-proven NASH and 31 with NAFLD diagnosed by ultrasonography). After 24 weeks, body weight, hemoglobin A1c (HbA1c), aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyl transpeptidase, body fat mass, and steatosis were significantly decreased compared to baseline measurements in patients with NASH. However, muscle mass was not reduced, and liver stiffness showed a statistically insignificant tendency to decrease. NAFLD patients also showed a significant reduction in body weight, HbA1c, AST, and ALT compared to baseline measurements. CONCLUSION: Ipragliflozin may be effective in patients with T2DM complicated by NAFLD.

The effectiveness of dapagliflozin for sleep-disordered breathing among Japanese patients with obesity and type 2 diabetes mellitus.

Weight reduction is important in patients with sleep-disordered breathing (SDB). In Japanese patients, slight weight reduction is effective for improving the severity of SDB. However, the effect of weight reduction after administration of sodium glucose co-transporter 2 (SGLT2) inhibitor for SDB remains unclear. The aim of this study was to evaluate the improvement of SDB from baseline after administration of dapagliflozin (5 mg) once daily for 24 weeks among Japanese patients with obesity and type 2 diabetes mellitus. Thirty Japanese patients with type 2 diabetes mellitus and SDB were enrolled in a 24-week, prospective, open-label, single-arm, multicentre trial. SDB was defined as at least five 3% oxygen desaturation index (ODI) events per hour, and moderate to severe SDB was defined as at least 15 ODI events per hour. The primary endpoint was the change in 3% ODI between before dapagliflozin administration and at 24 weeks. The prevalence of moderate to severe SDB was 20% in the present study. After administration of dapagliflozin, fasting glucose, HbA1c, aspartate aminotransferase, total cholesterol, low-density lipoprotein cholesterol, and estimated globular filtration rate decreased significantly. The improvement of 3% ODI was observed in patients with moderate to severe SDB but not mild SDB (from 25.0 ± 3.8 at baseline to 18.5 ± 6.1 at 24 weeks, p = 0.017). In conclusion, dapagliflozin might improve moderate to severe SDB but not mild SDB in Japanese patients with obesity and type 2 diabetes mellitus.

Low Urine pH Is Associated with Non-alcoholic Fatty Liver Disease: A Community-based Cross-sectional Study.

Objective Low urine pH is associated with several metabolic diseases, such as dyslipidemia, diabetes, and metabolic syndrome. However, the association between low urine pH and non-alcoholic fatty liver disease (NAFLD) remains unknown. Therefore, we conducted a community-based cross-sectional study to investigate this association. Methods Between April 2013 and March 2014, the records of 4,945 Japanese subjects who had undergone annual health checkups were reviewed to identify subjects who met the diagnostic criteria for NAFLD. Patients Based on urine pH, the participants were classified into four groups; a low urine pH was defined as ≤5.5. Of the 3,411 subjects who qualified for enrollment, 1,028 met the diagnostic criteria for NAFLD. Results The prevalence of NAFLD was significantly increased with decreasing urine pH in both men and women (p<0.01 and p=0.02, respectively). A multivariate analysis, including adjustments for age, metabolic markers, and the renal function, showed a significant association between low urine pH and NAFLD in men and women (odds ratio, 1.37; 95% confidence interval, 1.01-1.85, p=0.04 and odds ratio, 1.73; 95% confidence interval, 1.15-2.62, p<0.01, respectively). Conclusion Our study indicates that NAFLD is associated with a low urine pH in both sexes, findings that might help clinicians identify patients at high risk for NAFLD.